工程生物催化合成β-N-替代-α-氨基酸的生物催化合成
Jairo Villalona1, Peyton M Higgins1, Andrew R Buller1
1Department of Chemistry, University of Wisconsin, Madison, 1101 University Avenue, Madison, WI 53706, USA.
Angewandte Chemie (International ed. in English)
|August 25, 2023
概括
研究人员通过生物催化N替代工程调研了托合成酶 (TrpB),通过生物催化N替代制造出新型的α,β-氨酸. 这种方法可以在克尺度上合成药物发现和化学生物学中有价值的构建模块.
科学领域:
- 生物催化剂是一种生物催化剂.
- 酶工程是什么? 酶工程是什么?
- 有机合成 有机合成
背景情况:
- 非正规氨基酸 (ncAAs) 对于开发新药和新材料至关重要.
- 酶工程已经推进了β替代氨基酸的合成.
- 合成α,β-氨基酸的生物催化方法仍然有限.
研究的目的:
- 为了设计托合成酶 (TrpB) 的β子单元,以增强与多种氨基核友的活性.
- 开发生物催化N替代反应以产生α,β-氨酸.
- 为了使这些新型氨基酸能够在克尺度上进行合成.
主要方法:
- 托合成酶 (TrpB) 的定向演变.
- 机械分析以了解产量限制.
- 使用l-胺来抑制产品重新进入的优化.
- 测试了十几个氨酸核友.
主要成果:
- 工程TrpB证明了与各种氨基核的改善活性.
- 产品的重新进入和分解被确定为产量限制因素.
- 添加l-氨酸成功抑制了产品的重新进入,促进了合成.
- 用氨基胺实现了β替代氨基酸的格拉姆尺度合成.
结论:
- 工程TrpB为α,β-氨基酸提供了生物催化途径.
- 添加l-Serine是提高准备合成产量的关键策略.
- 这些新型氨基酸代表了化学生物学和药物化学的宝贵构建基.
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